In this 2-year AARA grant application, we propose to develop, construct, and evaluate a prototype SPECT/MRI system for simultaneous high-resolution molecular SPECT/MR imaging of small animals, with the potential of further developing into a human brain SPECT/MRI system. The main innovations include the use of state-of-the-art MR compatible cadmium zinc telluride (CZT) detector modules developed by our industrial partner, Gamma Medica-Ideas (GMI). The new CZT detectors have small sub-millimeter resolvable pixel size that allows acquisition of high-resolution SPECT projection data. A ring-type SPECT subunit will be developed based on five CZT based cameras each consists of a 5x5 array of 2.54cmx2.54cm CZT detector modules. The cameras will connected seamlessly to form a ring SPECT subunit that will fit inside a 3T Philips MRI system allowing high-resolution SPECT imaging for small animals as well as potential development of a human brain SPECT/MRI system, for simultaneous acquisition of SPECT/MRI data. A cylindrical collimator with an array of multi-pinhole apertures that surrounds the small animal will be developed and a birdcage RF coil will be designed and constructed that is attached to the inside surface of the collimator cylinder. Multi-pinhole images of the small animal are projected onto the contiguous detector surface. Also, shimming methods, quantitative multi-pinhole SPECT image reconstruction methods, optimized MR pulse sequences and image fusion methods will be developed for artifact-free co-registered SPECT/MR images. The Johns Hopkins University (JHU) team of investigators comprises strong expertise in high-resolution SPECT instrumentation, simulation tools and quantitative image reconstruction methods and in MR imaging including RF coil design, shimming for magnetic field uniformity, MR pulse sequences, MR data acquisition methods and image reconstruction and processing methods. The proposed research will involve (1) development of high-resolution MR compatible CZT detectors for SPECT imaging, (2) development of optimized RF transmit/receive coils, shimming methods and MRI pulse sequences for artifact-free high-resolution small animal MR imaging using the Philips 3T MRI system in the presence of the SPECT subunit, (3) development of an optimized MR compatible SPECT subunit and image reconstruction methods for artifact-free SPECT images inside the 3T MRI system, and (4) preliminary evaluation of the SPECT/MR system using physical phantom and simulation studies.